2-(Trifluoromethyl)oxirane → 3-[[3-(4-Chloro-3-ethylphenoxy)phenyl][3-cyclohexylmethyl]amino]-1,1,1-trifluoro-2-propanol
Reaction equation
[Cl:1][C:2]1[CH:15]=[CH:14][C:5]([O:6][C:7]2[CH:8]=[C:9]([CH:11]=[CH:12][CH:13]=2)[NH2:10])=[CH:4][C:3]=1[CH2:16][CH3:17].[F:18][C:19]([F:24])([F:23])[CH:20]1[O:22][CH2:21]1>>[Cl:1][C:2]1[CH:15]=[CH:14][C:5]([O:6][C:7]2[CH:8]=[C:9]([N:10]([CH2:16][CH:3]3[CH2:4][CH2:5][CH2:14][CH2:15][CH2:2]3)[CH2:21][CH:20]([OH:22])[C:19]([F:24])([F:23])[F:18])[CH:11]=[CH:12][CH:13]=2)=[CH:4][C:3]=1[CH2:16][CH3:17]Participants
Conditions
- Temperature
- 90 °C
Procedure
EX-18C) The 3-(4-chloro-3-ethylphenoxy)aniline (0.545 g, 0.002 mol) product from EX-18B was mixed with neat 3,3,3-trifluoro-1,2-epoxypropane (0.220 g, 0.002 mol) in a pressurized vial. The resulting mixture was heated at 90° C. for 18 h, cooled, and the excess 3,3,3-trifluoro-1,2-epoxypropane was removed in vacuo. The crude product was purified by flash column chromatography on silica gel eluting with 1:4 ethyl acetate in hexane to give 0.254 g (35%) of the desired 3-[[3-(4-chloro-3-ethyl-phenoxy)phenyl]amino]-1,1,1-trifluoro-2-propanol product as a pure orange oil. Anal calcd. for C17H17NOF3Cl: C, 56.75; H, 4.76; N, 3.89. Found: C, 56.72; H, 4.70; N, 3.85. HRMS calcd.: 360.0978 [M+H]+, found: 360.0969. 1H NMR (CDCl3) δ 1.50 (t, 3H), 2.72 (m, 2H), 3.36 (m, 1H), 3.54 (m, 1H), 4.20 (m, 1H), 6.42 (m, 2H), 6.81 (dd, 1H), 6.94 (d, 1H), 7.18 (d, 1H), 7.25 (m, 2H).
Workup
- temperaturecooled
- customthe excess 3,3,3-trifluoro-1,2-epoxypropane was removed in vacuo
- customThe crude product was purified by flash column chromatography on silica gel eluting with 1:4 ethyl acetate in hexane
Sources & evidence
- ORD record
- ord-b79ecc8964fe4903833b37c81ac1b79d
- Source dataset
- uspto-grants-2004_09
- Patent number
- US06787570B2
Reaction notes
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